Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. Export

@article{citeulike:5096930, abstract = {BACKGROUND: Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown. METHODS: The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed. RESULTS: Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS. CONCLUSIONS: Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS.}, author = {Avirutnan, P. and Punyadee, N. and Noisakran, S. and Komoltri, C. and Thiemmeca, S. and Auethavornanan, K. and Jairungsri, A. and Kanlaya, R. and Tangthawornchaikul, N. and Puttikhunt, C. and Pattanakitsakul, S. N. and Yenchitsomanus, P. T. and Mongkolsapaya, J. and Kasinrerk, W. and Sittisombut, N. and Husmann, M. and Blettner, M. and Vasanawathana, S. and Bhakdi, S. and Malasit, P.}, citeulike-article-id = {5096930}, citeulike-linkout-0 = {http://dx.doi.org/10.1086/500949}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16544248}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16544248}, day = {15}, doi = {10.1086/500949}, issn = {0022-1899}, journal = {The Journal of infectious diseases}, keywords = {complement, dengue, ns1, vascular}, month = {April}, number = {8}, pages = {1078--1088}, posted-at = {2009-07-09 17:56:27}, priority = {2}, title = {Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement.}, url = {http://dx.doi.org/10.1086/500949}, volume = {193}, year = {2006} }

TY - JOUR ID - citeulike:5096930 L3 - citeulike-article-id:5096930 N2 - BACKGROUND: Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown. METHODS: The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed. RESULTS: Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS. CONCLUSIONS: Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS. IS - 8 JF - The Journal of infectious diseases SN - 0022-1899 EP - 1088 TI - Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. VL - 193 SP - 1078 KW - complement KW - dengue KW - ns1 KW - vascular AU - Avirutnan, P AU - Punyadee, N AU - Noisakran, S AU - Komoltri, C AU - Thiemmeca, S AU - Auethavornanan, K AU - Jairungsri, A AU - Kanlaya, R AU - Tangthawornchaikul, N AU - Puttikhunt, C AU - Pattanakitsakul, SN AU - Yenchitsomanus, PT AU - Mongkolsapaya, J AU - Kasinrerk, W AU - Sittisombut, N AU - Husmann, M AU - Blettner, M AU - Vasanawathana, S AU - Bhakdi, S AU - Malasit, P PY - 2006/04/15/ UR - http://dx.doi.org/10.1086/500949 ER -